Using a functional enzyme model to understand the chemistry behind hydrogen sulfide induced hibernation

Abstract

The toxic gas H 2 S is produced by enzymes in the body. At moderate concentrations, H 2 S elicits physiological effects similar to hibernation. Herein, we describe experiments that imply that the phenomenon probably results from reversible inhibition of the enzyme cytochrome c oxidase (CcO), which reduces oxygen during respiration. A functional model of the oxygen-reducing site in CcO was used to explore the effects of H 2 S during respiration. Spectroscopic analyses showed that the model binds two molecules of H2S. The electro-catalytic reduction of oxygen is reversibly inhibited by H 2 S concentrations similar to those that induce hibernation. This phenomenon derives from a weak, reversible binding of H 2 S to the Fe II porphyrin, which mimics heme a 3 in CcO's active site. No inhibition of CcO is detected at lower H 2 S concentrations. Nevertheless, at lower concentrations, H 2 S could have other biological effects on CcO. For example, H 2 S rapidly reduces Fe III and Cu II in both the oxidized form of this functional model and in CcO itself. H 2 S also reduces CcO's biological reductant, cytochrome c , which normally derives its reducing equivalents from food metabolism. Consequently, it is speculated that H 2 S might also serve as a source of electrons during periods of hibernation when food supplies are low.